Predictors of Coronary Plaque Erosion in Current and Non-Current Smokers With ST-Segment Elevation Myocardial Infarction　― An Optical Coherence Tomography Study ―

Yidan Wang; Chao Fang; Shaotao Zhang; Lulu Li; Jifei Wang; Yanwei Yin; Yini Wang; Huai Yu; Guo Wei; Xiling Zhang; Junchen Guo; Senqing Jiang; Fangmeng Lei; Jia Lu; Yingfeng Tu; Jingbo Hou; Jiannan Dai; Bo Yu

doi:10.1253/circj.CJ-20-0890

Abstract

Background: Smoking is an important risk factor of plaque erosion. This study aimed to investigate the predictors of plaque erosion in current and non-current smokers presenting with ST-segment elevation myocardial infarction (STEMI).

Methods and Results: A total of 1,320 STEMI patients with culprit plaque rupture or plaque erosion detected by pre-intervention optical coherence tomography were divided into a current smoking group (n=715) and non-current smoking group (n=605). Plaque erosion accounted for 30.8% (220/715) of culprit lesions in the current smokers and 21.2% (128/605) in the non-current smokers. Multivariable analysis showed age <50 years, single-vessel disease and the absence of dyslipidemia were independently associated with plaque erosion rather than plaque rupture, regardless of smoking status. In current smokers, diabetes mellitus (odds ratio [OR]: 0.29; 95% confidence interval [CI]: 0.10–0.83; P=0.021) was negatively associated with plaque erosion as compared with plaque rupture. In non-current smokers, minimal lumen area (MLA, OR: 1.37; 95% CI: 1.16–1.62; P<0.001) and nearby bifurcation (OR: 3.20; 95% CI: 1.98–5.16; P<0.001) were positively related to plaque erosion, but not plaque rupture.

Conclusions: In patients with STEMI, the presence of diabetes mellitus significantly increased the risk of rupture-based STEMI but may not have reduced the risk of plaque erosion-based STEMI in current smokers. Nearby bifurcation and larger MLA were associated with plaque erosion in non-current smokers.

Cigarette smoking, a major risk factor for cardiovascular disease, facilitates the development of atherosclerosis.¹ Previous research has demonstrated that smoking can induce plaque instability, which may lead to plaque rupture.²^–⁶ Intriguingly, plaque erosion, the other major mechanism for coronary thrombosis without fibrous cap disruption, is more frequently observed in cigarette smokers.⁷^,⁸ Autopsy and optical coherence tomography (OCT) studies have demonstrated that plaque erosion is responsible for approximately one-third of patients with acute coronary syndromes (ACS), including ST-segment elevation myocardial infarction (STEMI).⁹^–¹² Cigarette smoking may contribute to coronary endothelial apoptosis and promote thrombus formation, resulting in acute myocardial ischemia.¹³^–¹⁵

However, the relationship between current smoking status and plaque erosion has not been systematically investigated. Therefore, the present study aimed to investigate the clinical and coronary lesion predictors of plaque erosion (vs. plaque rupture)-based STEMI among current and non-current smokers by using OCT.

Methods

Study Design and Patients

We retrospectively collected consecutive patients with STEMI who underwent OCT imaging during primary percutaneous coronary intervention between August 2014 and December 2017. As shown in the study flow chart (Figure 1), a total of 4,284 patients presented with STEMI, and of them, 2,624 did not undergo OCT imaging for the following reasons: cardiogenic shock, severe kidney and/or liver dysfunction, allergy to contrast media, contraindications for antithrombotic therapy, left main disease, chronic total occlusion, and extremely tortuous and heavily calcified vessels. Therefore, we enrolled 1,660 eligible consecutive patients who underwent OCT imaging during emergency intervention, comprising 581 patients from a prospective OCT registry (ClinicalTrials.gov; NCT03084991), and 1,079 patients who were retrospectively collected. There were 218 patients who were further excluded from analysis for the following reasons: (1) predilation before OCT examination (n=31), (2) poor OCT image quality or massive thrombus (n=129), (3) Intrastent thrombosis or neoatherosclerosis (n=58), (4) coronary dissection (n=53), (5) tight stenosis (n=24), (6) coronary spasm or culprit lesion not identified (n=22), and (7) calcified nodules (n=23). Patients were divided into a current smoking group (n=715) with culprit plaque rupture (n=495)/plaque erosion (n=220), and a non-current smoking group (n=605) with culprit plaque rupture (n=477)/plaque erosion (n=128). Current smokers were defined as active smoking over the past month, and non-current smokers were defined as patients who had quit at least 1 month before evaluation and those who had never smoked.¹⁶^,¹⁷ The diagnosis of STEMI and identification of the culprit lesion are detailed in Supplementary File.¹⁰

Figure 1.

Study flow chart. OCT, optical coherence tomography; STEMI, ST-segment elevation myocardial infarction.

The study was approved by the Ethics Committee of the 2nd Affiliated Hospital of Harbin Medical University (reference no. KY2017-249), and all patients provided written informed consent.

Angiographic Analysis

The quantitative coronary angiography data was analyzed using the Cardiovascular Angiography Analysis System (CAAS, 5.10, Pie Medical Imaging B.V., Maastricht, The Netherlands) by an independent investigator (S.Z.). Lesion location, lesion length, minimal lumen diameter (MLD), reference vessel diameter (RVD), diameter stenosis (DS), and initial Thrombolysis in Myocardial Infarction (TIMI) flow were measured.

OCT Image Acquisition and Analysis

OCT imaging was performed at the discretion of an interventional cardiologist and using a commercially available frequency-domain OCT system (C7-XR or ILUMIEN OPTIS, Abbott Vascular, Santa Clara, CA, USA). All OCT images were analyzed in the imaging core laboratory by 2 experienced investigators (C.F. and J.D.) who were blinded to the patients’ information. When there was disagreement between the investigators, a consensus reading was performed by a third investigator.

The culprit lesion was diagnosed using established OCT criteria.¹⁰ Plaque rupture was identified as the presence of fibrous cap discontinuity with a cavity within the plaque.¹⁸ Plaque erosion was identified by the presence of attached thrombus overlying an intact and visualized plaque, luminal surface irregularity at the culprit lesion in the absence of thrombus, or attenuation of the underlying plaque by thrombus without superficial lipid or calcification immediately proximal or distal to the site of thrombus.¹⁰ Plaque rupture and plaque erosion are showed in Supplementary Figure.

The inter- and intraobserver kappa coefficients for plaque erosion and plaque rupture were 0.865 and 0.871, respectively, and 0.893 and 0.915, respectively.

Minimal lumen area (MLA) was the minimum value of the lumen area along the culprit lesion.¹⁹ Plaques were classified as fibrous (homogeneous and high-backscattering region) or lipid (low-signal region with a diffuse border).¹⁸^,¹⁹ For lipid plaque, lipid core length was recorded in the longitudinal view, and the lipid arc was measured in each 1 mm on the cross-sectional view; the maximal lipid arc and mean lipid arc were then calculated.¹⁸ Lipid-rich plaque (LRP) was identified as plaque with a lipid arc >90° on any cross-section.²⁰ The minimal fibrous cap thickness (FCT) was measured 3 times at its thinnest to obtain a mean value.¹⁸ Thin-cap fibroatheroma (TCFA) was identified as LRP with minimal FCT <65 μm.¹⁰^,¹⁸ When a low-backscattering heterogeneous region with well-delineated border underlying a plaque was detect, it was recorded as calcification. Microvessels were defined as signal-poor voids that were sharply delineated in multiple contiguous frames.¹⁸ Macrophage accumulation was defined as signal-rich, distinct or confluent punctuate regions with heterogeneous backward shadowing.¹⁹ Cholesterol crystals were recorded as thin, linear regions of high intensity, usually associated with a fibrous cap or necrotic core.¹⁹ Nearby bifurcation was predefined as erosion or rupture located within 5 mm proximal or distal to a side branch with an orifice diameter >1.0 mm measured by OCT.¹⁶ For plaque erosion and plaque rupture, the MLA site and the location of the maximal rupture cavity were selected respectively to measure the distance between erosion and rupture and nearby bifurcation.²¹

Statistical Analysis

Statistical analyses were performed using SPSS version 25.0 and analyzed by an independent statistician (L.L.). Kolmogorov-Smirnov test was used to test the normality of variables. Continuous variables are shown as mean±standard deviation (SD) for normally distributed data or as median (25–75th percentiles) for non-normally distributed data. The significance of variables was conducted using Student’s t-test for normally distributed continuous variables and Mann-Whitney U-test for non-normally distributed continuous variables. Categorical data are presented as counts (proportions) and compared using the χ² or Fisher’s exact test. Age <50 years was considered as a categorical variable indicating premenopausal status and has been used as the cutoff in previous studies.²²^,²³ The correlation analysis between plaque erosion and the clinical, angiographic, characteristics of patients was based on the results of univariate analysis and was analyzed using a multivariate logistic regression model (stepwise analysis). Variables with P<0.1 in the univariate analysis were tested with a multivariable model. A kappa test was used to evaluate the inter- and intraobserver variability for qualitative OCT assessment. The reliability of continuous variables in the OCT measurements was expressed as the intraclass correlation coefficient. A two-tailed P value <0.05 was considered statistically significant.

Results

Incidence of Plaque Erosion and Clinical Characteristics

Plaque erosion was identified in 30.8% (220/715) of current smokers and 21.2% (128/605) of non-current smokers. In the current smoking group, patients with culprit plaque erosion were younger, predominately male, and had less coronary risk factors, including diabetes mellitus, hypertension, hyperlipidemia, and chronic kidney disease (CKD), than those with plaque rupture. In the non-current smoking group, patients with plaque erosion were also younger and had less frequency of hypertension and dyslipidemia than those with plaque rupture. The detailed clinical features of the 2 groups were summarized in Table 1.

Table 1. Clinical Features

Variables	Current smoking group			Non-current smoking group
Variables	Plaque rupture (n=495)	Plaque erosion (n=220)	P value	Plaque rupture (n=477)	Plaque erosion (n=128)	P value
Age, years	55.9±10.4	52.7±9.8	<0.001*	61.2±11.0	57.5±12.3	0.003*
<50 years, n (%)	154 (31.1)	89 (40.5)	0.015*	87 (18.2)	39 (30.5)	0.002*
Men, n (%)	400 (80.8)	194 (88.2)	0.015*	289 (60.6)	82 (64.1)	0.473
Coronary risk factors
Diabetes mellitus, n (%)	109 (22.0)	30 (13.6)	0.009*	121 (25.4)	22 (17.2)	0.053
Hypertension, n (%)	230 (46.5)	70 (31.8)	<0.001*	266 (55.8)	54 (42.2)	0.006*
Dyslipidemia, n (%)	343 (69.3)	114 (51.8)	<0.001*	325 (68.6)	52 (40.6)	<0.001*
CKD, n (%)	43 (8.7)	8 (3.6)	0.015*	66 (13.8)	12 (9.4)	0.181
Laboratory tests
TC, mg/dL	187.2±40.5	178.7±39.7	0.009*	186.3±42.6	176.9±47.5	0.045*
TG, mg/dL	142.6 (100.1, 182.5)	127.6 (86.8, 161.0)	<0.001*	138.1 (93.0, 182.5)	124.0 (87.7, 151.0)	0.018*
TC/HDL-C ratio, mg/dL	4.0±1.1	3.7±0.9	<0.001*	3.9±1.5	3.7±1.6	0.198
HDL-C, mg/dL	48.1±10.5	50.3±11.3	0.012*	50.0±13.5	50.2±11.2	0.893
LDL-C, mg/dL	121.1±35.3	115.1±36.5	0.039*	118.5±36.9	109.2±44.5	0.030*
hs-CRP, mg/L	5.4 (2.2, 12.0)	4.5 (1.9, 11.6)	0.144	5.2 (2.0, 11.9)	6.1 (1.9, 12.0)	0.898

Values are presented as n (%), mean±SD, or median (25–75th percentiles). *P<0.05 was considered statistically significant. CKD, chronic kidney disease; HDL-C, high-density lipoprotein cholesterol; hs-CRP, high-sensitivity C-reactive protein; LDL-C, low-density lipoprotein; SD, standard deviation; TC, total cholesterol; TG, triglyceride cholesterol.

Angiographic Findings

The angiographic findings of the culprit lesions are presented in Table 2. In the non-current smoking group, plaque erosion was more frequently located in the left anterior descending artery (LAD) than plaque rupture. The incidence of multivessel disease with plaque erosion was lower than with plaque rupture. DS was less severe in plaque erosion vs. plaque rupture. Current smokers had similar results as non-current smokers.

Table 2. Angiographic Findings

Variables	Current smoking group			Non-current smoking group
Variables	Plaque rupture (n=495)	Plaque erosion (n=220)	P value	Plaque rupture (n=477)	Plaque erosion (n=128)	P value
Culprit vessel, n (%)			0.001*			0.001*
LAD	227 (45.9)	131 (59.5)		230 (48.2)	86 (62.7)
LCX	51 (10.3)	23 (10.5)		48 (10.1)	5 (3.9)
RCA	217 (43.8)	66 (30.0)		199 (41.7)	37 (28.9)
Culprit lesion site, n (%)			0.372			0.395
Proximal segment	184 (37.2)	94 (42.7)		211 (44.2)	65 (50.8)
Mid segment	215 (43.3)	87 (35.9)		184 (38.6)	45 (35.2)
Distal segment	96 (19.4)	39 (17.7)		82 (17.2)	18 (14.1)
Distance to the ostium, mm	35.4±21.2	31.3±21.7	0.019*	33.4±21.0	28.2±21.8	0.013*
Multivessel disease, n (%)	260 (52.5)	77 (35.0)	<0.001*	282 (59.1)	39 (30.5)	<0.001*
Initial TIMI flow ≤1, n (%)	387 (78.2)	139 (63.2)	<0.001*	367 (76.9)	87 (68.0)	0.037*
Manual thrombectomy, n (%)	446 (90.1)	179 (81.4)	0.001*	426 (89.3)	104 (81.3)	0.014*
RVD, mm	2.9±0.6	3.1±0.6	0.011*	3.0±0.6	3.1±0.5	0.247
MLD, mm	0.0 (0.0, 0.5)	0.2 (0.0, 0.9)	<0.001*	0.0 (0.0, 0.6)	0.0 (0.2, 0.8)	0.013*
DS, %	93.6±12.5	86.9±19.3	<0.001*	93.1±13.0	88.7±17.0	0.009*
Lesion length, mm	17.3±8.3	17.9±8.8	0.606	17.4±8.0	17.8±8.5	0.790

Values expressed as n (%), mean±SD, or median (25–75th percentiles). *P<0.05 was considered statistically significant. DS, diameter stenosis; LAD, left anterior descending artery; LCX, left circumflex artery; MLD, minimal lumen diameter; RCA, right coronary artery; RVD, reference vessel diameter; SD, standard deviation; TIMI, Thrombolysis in Myocardial Infarction.

OCT Findings

The OCT findings of the 2 groups are presented in Table 3. OCT analysis showed significant differences in culprit lesion morphology between plaque rupture and plaque erosion, regardless of current smoking status, including higher likelihood of being adjacent to nearby bifurcation, higher incidence of fibrous plaque, larger MLA, thicker FCT and lower prevalence of LRP, TCFA, macrophages, microvessels, cholesterol crystals, calcification, and shorter lipid core length, smaller maximal and mean lipid arc in plaque erosion compared with plaque rupture.

Table 3. Optical Coherence Tomography Analysis

Variables	Current smoking group			Non-current smoking group
Variables	Plaque rupture (n=495)	Plaque erosion (n=220)	P value	Plaque rupture (n=477)	Plaque erosion (n=128)	P value
MLA, mm²	1.7 (1.3, 2.2)	1.9 (1.5, 2.9)	<0.001*	1.6 (1.3, 2.0)	1.8 (1.4, 2.7)	<0.001*
Plaque type, n (%)			<0.001*			<0.001*
Lipid	495 (100.0)	102 (46.4)		477 (100.0)	72 (56.3)
Fibrous	0 (0.0)	118 (53.6)		0 (0.0)	56 (43.8)
LRP, n (%)	493 (99.6)	98 (44.5)	<0.001*	474 (99.4)	69 (53.9)	<0.001*
Minimal FCT, μm	46.0±16.4	92.2±37.3	<0.001*	45.5±15.2	92.2±43.0	<0.001*
Lipid core length, mm	13.7±6.3	10.1±4.8	<0.001*	13.4±6.6	11.0±5.9	0.002*
Mean lipid arc, °	238.5±45.8	222.0±47.5	0.002*	244.5±46.6	217.6±50.3	<0.001*
Maximal lipid arc, °	333.6±48.6	303.3±61.3	<0.001*	334.1±46.4	298.7±67.1	<0.001*
TCFA, n (%)	441 (89.1)	22 (10.0)	<0.001*	432 (90.6)	25 (19.5)	<0.001*
Calcification, n (%)	220 (44.4)	64 (29.1)	<0.001*	250 (52.4)	41 (32.0)	<0.001*
Microvessels, n (%)	233 (47.1)	76 (34.5)	0.002*	236 (49.5)	40 (31.3)	<0.001*
Macrophages, n (%)	453 (91.5)	117 (53.2)	<0.001*	434 (91.4)	73 (58.4)	<0.001*
Cholesterol crystals, n (%)	191 (38.6)	41 (18.6)	<0.001*	201 (42.1)	30 (23.4)	<0.001*
Nearby bifurcation, n (%)	177 (35.8)	134 (60.9)	<0.001*	169 (35.4)	84 (65.6)	<0.001*

Values are presented as n (%), mean±SD, or median (25th–75th percentile). *P<0.05 was considered statistically significant. FCT, fibrous cap thickness; LRP, lipid-rich plaque; MLA, minimal lumen area; SD, standard deviation; TCFA, thin-cap fibroatheroma.

Multivariate Analyses of Plaque Erosion in the Current Smoking and Non-Current Smoking STEMI Patients

Univariate regression analysis of the current and non-current smoking groups were tested: age <50 years, male, diabetes mellitus, hypertension, dyslipidemia, CKD, total cholesterol (TC), triglyceride cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), TC/HDL-C ratio, culprit lesion in LAD, distance to the ostium, multivessel disease, initial TIMI flow ≤1, manual thrombectomy, RVD, DS, MLA, and nearby bifurcation as shown in Supplementary Table 1. In the multivariable analysis, age <50 years, lack of diabetes mellitus, lack of dyslipidemia, and lack of multivessel disease were significantly associated with plaque erosion in the current smoking group, whereas age <50 years, the absence of dyslipidemia, lack of multivessel disease, larger MLA, and nearby bifurcation were significantly associated with plaque erosion in the non-current smoking group as shown in Supplementary Table 2. Variables with a P<0.05 in the multivariate regression analysis of factors independently related to plaque erosion in the current and non-current smoking groups are shown in Figure 2A,B. Multivariable analysis showed that age <50 years, single-vessel disease and the absence of dyslipidemia were independently associated with plaque erosion rather than plaque rupture, regardless of smoking status. In current smokers, diabetes mellitus was negatively associated with plaque erosion as compared with plaque rupture. In non-current smokers, larger MLA and nearby bifurcation were positively related to plaque erosion, but not plaque rupture.

Figure 2.

Multivariate regression analysis of factors independently related to plaque erosion-based STEMI in (A) the current and (B) the non-current smoking group. OR for MLA was calculated for each1.0-mm² increase. CI, confidence interval; MLA, minimal lumen area; OR, odds ratio; STEMI, ST-segment elevation myocardial infarction.

Discussion

The main findings of the present study were as follows: (1) common predictors, including age <50 years, absence of dyslipidemia, and single-vessel disease, were independently related to culprit plaque erosion regardless of smoking status; (2) the presence of diabetes mellitus significantly increased the risk of rupture-based STEMI but may not reduce the risk of plaque erosion-based STEMI in current smokers; and (3) nearby bifurcation and larger MLA were associated with plaque erosion in non-current smokers but not in current smokers. We have summarized the critical findings in Figure 3.

Figure 3.

Take home message. Predictors of plaque erosion (vs. plaque rupture)-based STEMI varies under different current smoking status. In patients with STEMI, age <50 years, single-vessel disease and the absence of dyslipidemia are independently associated with plaque erosion rather than plaque rupture, regardless of smoking status. In current smokers, diabetes mellitus is negatively associated with plaque erosion as compared with plaque rupture. In non-current smokers, larger MLA and nearby bifurcation are positively related to plaque erosion, but not plaque rupture. Plaque rupture: white arrows indicate ruptured fibrous cap. The contents of the ruptured plaque have been partially washed away by flushing, leaving behind a cavity (white asterisk). The red asterisk mark indicates guidewire artifact. Plaque erosion: white arrows indicate a thrombus on the irregular luminal surface. There is no evidence of rupture. The red asterisk indicates guidewire artifact. MLA, minimal lumen area; STEMI, ST-segment elevation myocardial infarction.

Common Predictors of Culprit Plaque Erosion Regardless of Smoking Status

Plaque erosion causing STEMI onset had common predictors in the current and non-current smoking groups, including age <50 years, absence of dyslipidemia, and single-vessel disease. In line with our study, other OCT studies¹⁶^,²⁴ showed that age, dyslipidemia, and multivessel disease were independently associated with plaque erosion in patients with ACS. Dyslipidemia, and multivessel disease were less frequent with plaque erosion, but younger age was associated with plaque erosion, regardless of smoking status.¹⁶^,²⁴ Previous pathology studies have reported that acute rupture is more frequent in the sudden cardiac death of patients aged >50 years, whereas plaque erosion is more common in those aged <50 years.⁷^,²³^,²⁵ Dyslipidemia is a predictor of acute coronary thrombosis, and ruptured plaque formation is an inflammatory process related to lipid deposition.²⁶ Autopsy studies have revealed that a lower TC level, and a lower TC/HDL-C ratio is specifically associated with plaque erosion, compared with plaque rupture.²³^,²⁵^,²⁷ These findings are consistent with our result that the absence of dyslipidemia was associated with plaque erosion. The angiographic finding of plaque erosion was more frequent with single-vessel disease, and patients with plaque erosion had less complex angiographic features at both the 3-vessel coronary level and the culprit lesion level.¹⁶^,²⁴^,²⁸

Diabetes Mellitus Increased Plaque Rupture-Based STEMI in Current Smokers But Not Non-Current Smokers

The presence of diabetes mellitus significantly increased the risk of rupture-based STEMI but may not have reduced the risk of plaque erosion-based STEMI in the current smoking group. Diabetes mellitus is associated with accelerated coronary atherosclerosis because of the accentuated proinflammatory and prothrombotic status induced by the associated metabolic abnormalities.²⁹ OCT evidence suggests that diabetes mellitus can predict TCFA, the precursor of plaque rupture.³⁰ Furthermore, cigarette smoking induces insulin resistance and hyperinsulinemia.³¹ Previous intravascular imaging studies found that the increased insulin resistance and hyperinsulinemia induced by smoking were associated with LRPs, which increases the occurrence of plaque rupture.³²^–³⁴ The combined action of smoking and diabetes mellitus contributes to current smokers with diabetes mellitus having a high risk of plaque rupture. Those findings support our finding that diabetes mellitus increased the risk of rupture-based STEMI but may not have reduced the risk of plaque erosion-based STEMI in the current smoking group.

Nearby Bifurcation and Larger MLA Independently Associated With Plaque Erosion in Non-Current Smokers But Not Current Smokers

As local anatomic factors, nearby bifurcation and larger MLA promoted erosion-based STEMI in the non-current smokers, but were not associated with erosion-based STEMI in the current smokers. These findings suggested that hemodynamic factors play a leading role in the formation of plaque erosion in non-current smokers.

For current smokers, smoking as a chemical factor that contributes to systemic effects may lead to an imbalance in supply and demand of oxygen in the coronary arteries, leading to hypoxia, which can damage endothelial cells and subsequent thrombosis, causing plaque erosion.³⁵ That may be the reason why nearby bifurcation and larger MLA did not have a significant effect on plaque erosion in current smokers. For non-current smokers, our study found that local hemodynamic factors, including nearby bifurcation and larger MLA, were related to plaque erosion, but not plaque rupture. This discrepancy may be due to different thrombus formation between current and non-current smokers.

Nearby bifurcation promoted erosion-based STEMI in non-current smokers, but was not associated with plaque erosion in the current smokers. Plaque erosion requires the combined action of hemodynamic disorders and plaque components. Intravascular imaging studies have identified nearby bifurcation as an important local hemodynamic factor of plaque erosion.¹⁶^,³⁶ Recently, it has shown that culprit lesions with intact fibrous cap are characterized by lower lipid content, less calcification, a thicker overlying fibrous cap, and location near a coronary bifurcation as compared with ruptured fibrous cap culprit lesions,³⁷ which is similar to our results. A nearby bifurcation will increase the endothelial sheer stress of the main vessel and further accelerate coronary endothelial injury, leading to thrombosis and plaque erosion.³⁸^,³⁹ Furthermore, in vivo local shear stress directly influences endothelial cell apoptosis in plaques associated with oscillatory shear stress downstream of the plaques, where plaque erosion tends to occur.⁴⁰^,⁴¹ Also, unlike plaque rupture that is mostly associated with TCFAs, plaque erosion is not only typically associated with fibrous plaque, but also lipid plaque including LRP and TCFA.⁴²^–⁴⁴ Hemodynamic changes around a nearby bifurcation accelerate the development of LRP. However, the formation of LRP is closely related to hemodynamic disorders and coronary risk factors, such as dyslipidemia, diabetes mellitus, hypertension and CKD, that are rarely seen in plaque erosion, and not all LRPs are the precursor of plaque rupture.²³^,⁴⁴^,⁴⁵ In the PROSPECT study, only <5% of TCFAs actually provoked a clinical event over a 3.4-year follow-up.⁴⁶ A recent study reported the expression of hyaluronidase 2 (HYAL2, an enzyme that degrades hyaluronan), which is associated with plaque erosion on OCT, is significantly enhanced in smokers.⁴⁷ HYAL2 was not expressed as much in non-current smokers, but local hemodynamic factors, such as nearby bifurcation, may play an important role in the formation of plaque erosion in non-current smokers.

The present study showed that in non-current smokers presenting with STEMI, a larger MLA was associated with culprit plaque erosion rather than plaque rupture. A culprit vessel with larger MLA frequently had fibrous plaques and were most prone to erosion; however, plaque rupture mainly occurred in lesions with heavy lipid load and thin fibrous cap.⁷^,⁹^,¹⁶^,⁴⁸ With lipid deposition, the lipid components gradually accumulate in the coronary arterial tree, the lumen diameter gradually shrinks even though plaque rupture appears to have extended into the lipid core.⁴⁹ This leads to coronary artery stenosis and consequent reduction of the MLA. Pathologic and intravascular imaging studies have not confirmed the association between plaque erosion and MLA in non-current smokers.

Clinical Significance

This study’s findings suggested that predictors of plaque erosion varied with different smoking status in patients with STEMI and expands clinicians’ understanding of clinical and lesion predictors of plaque erosion, especially in relation to smoking status. Recently, more and more researchers agree that plaque rupture and plaque erosion are different clinical entities.⁴³^,⁵⁰^,⁵¹ Several clinical studies have revealed that plaque erosion can be treated distinctively from plaque rupture.⁴⁴^,⁵⁰ However, the specific role of smoking in plaque rupture and plaque erosion is still obscure. By digging into this area, ideas for the prevention and management of STEMI patients with different current smoking status will be further explored for their individualized treatment. This in vivo OCT study may lay a foundation for future research. Comparative studies of plaque erosion-based STEMI and plaque rupture-based STEMI under different current smoking status may contribute to the goal of precision medicine and ultimately improve the prognosis of STEMI patients. Further research is needed to investigate the treatment and prognosis of STEMI patients based on different mechanisms and different smoking status.

Study Limitations

First, this was a single-center cohort study, which may lead to some bias in population selection. Second, the frequency and type of smoking among the current smokers were not recorded, nor were the smoking years of past smokers among the non-current smokers. Third, in this in vivo study, OCT was used as the diagnostic criteria for plaque erosion, rather than pathological diagnostic criteria. Due to the limitation of OCT resolution, the vascular endothelial cells of patients could not be observed. Fourth, OCT has limited penetration of lipid plaques, so could not be used to accurately evaluate plaque load, vascular remodeling and lesion eccentricity of culprit lesions; and because some calcified nodules are extremely tortuous and heavily calcified, which is a contraindication for OCT, exclusion of these patients may result in a low incidence of calcified nodules. Fifth, the predictive factors derived in this study were the characteristics of plaque erosion as compared with plaque rupture, but may not be essential for the development mechanisms of plaque erosion.

Conclusions

Predictors of plaque erosion (vs. plaque rupture)-based STEMI varied under different current smoking status. In patients with STEMI, age <50 years, single-vessel disease and the absence of dyslipidemia were independently associated with plaque erosion rather than plaque rupture, regardless of smoking status. In current smokers, diabetes mellitus was negatively associated with plaque erosion as compared with plaque rupture. In non-current smokers, larger MLA and nearby bifurcation were positively related to plaque erosion, but not plaque rupture. Compared with plaque rupture, the correlation between plaque erosion and current smoking status complements clinicians’ understanding of plaque erosion.

Acknowledgments

The authors sincerely thank all colleagues and patients who participated in this study.

Conflicts of Interest

The authors have no conflicts of interest to declare.

Data Availability

The deidentified participant data will not be shared.

Disclosures

B.Y. is an International Associate Editor of Circulation Journal.

Financial Support

This work was supported by National Key R&D Program of China (grant No. 2016YFC1301100 to B.Y.), National Natural Science Foundation of China (grant No. 81827806 to B.Y. and No. 82072091 to J.D.), and Natural Science Foundation of Heilongjiang Province (YQ2020H017 to J.D.).

The original study was approved by the Ethics Committee of the Second Affiliated Hospital of Harbin Medical University (reference no. KY2017-249).

Supplementary Files

Please find supplementary file(s);

http://dx.doi.org/10.1253/circj.CJ-20-0890

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